Social_affiliation_and_alcohol_drinking_in_rodents

描述（由申请人提供）：社会关系在酒精中毒和酗酒的发作和复发中起着重要作用，但酒精中毒和酒精滥用的这一方面尚未在啮齿动物中成功建模。最近，我们开发了使用草原田鼠（Microtus ochrogaster）研究消极（促进）和积极（抑制）的社会影响对酒精消费。具体来说，我们证明了这种物种的酒精偏好和大量的乙醇摄入，并表明成对居住的草原田鼠会影响彼此的饮酒。当田鼠被介绍给酒精对他们表现出更高的酒精偏好比当他们被介绍给酒精被单独安置。在这些配对中，一只田鼠影响（即，增加）其伴侣的酒精消费-建模促进对饮酒的影响。相比之下，在配对的高和低饮酒的田鼠，以前经历过酒精时，他们被单独圈养，田鼠与较高的基础摄入量往往会减少其饮酒，从而匹配其合作伙伴建模抑制社会影响。因此，草原田鼠可以作为第一个啮齿动物模型的影响，具体的人际关系对高酒精饮用的两个方向。我们假设，草原田鼠影响他们的合作伙伴的酒精消费率通过声学通信做人类，这种影响是由主导/顺从的关系，阿片类药物和加压素（AVP）系统。我们建议通过以下四个具体目标来检验这一假设。具体目标1：检验社会对饮酒的影响是否是通过同步饮酒发生的，是否受到显性-顺从互动的影响。具体目标2：测试USV是否有助于田鼠协调饮水，进一步提高我们模型的有效性。具体目标3：测试一种针对内源性阿片系统的酒精中毒既定药物治疗的疗效是否受社会影响的调节。具体目标4：为了测试已知调节草原田鼠社会关系的AVP系统是否有助于调节协调饮水。总之，这项工作将首次揭示调节啮齿动物模型中过度饮酒的社会影响的生物学机制。

DESCRIPTION (provided by applicant): Social affiliations play an important role in the onset and relapse of alcoholism and heavy drinking, yet this aspect of alcoholism and alcohol abuse has not been successfully modeled in rodents. Recently we developed the use of prairie voles (Microtus ochrogaster) to study negative (facilitating) and positive (inhibitory) social influences on alcohol consumption. Specifically, we demonstrated alcohol preference and heavy ethanol intake in this species, and showed that pair-housed prairie voles influence each other's drinking. When voles are introduced to alcohol in pairs they exhibit higher alcohol preference than when they are introduced to alcohol being single-housed. In these pairs, one vole influences (i.e., increases) alcohol consumption of its partner - modeling facilitating influences on alcohol drinking. In contrast, during pairing of high- and low-drinking voles that have previously experienced alcohol when they were single- housed, the vole with higher basal intake tends to decrease its drinking thereby matching its partner - modeling inhibitory social influences. Thus, the prairie vole could serve as the first rodent model of the effects of specific inter-personal affiliations on high alcohol drinking in both directions. We hypothesize that prairie voles influence their partner's rate of alcohol consumption via acoustic communication as do humans and that this influence is regulated by dominant/submissive relations, the opiate and the vasopressin (AVP) systems. We propose to test this hypothesis through following four Specific Aims. Specific Aim 1: To test whether the social influences on alcohol drinking occur by synchronizing alcohol drinking and are influenced by dominant-submissive interactions. Specific Aim 2: To test the whether USVs contribute to coordinated drinking in voles further increasing the validity of our model. Specific Aim 3: To test whether the efficacy of an established pharmacotherapy of alcoholism targeting the endogenous opiate system is modulated by social influences. Specific Aim 4: To test whether the AVP system known to regulate social affiliations in prairie voles contributes to regulation of coordinated drinking. Taken together this work will for the first time reveal information on the biological mechanisms regulating social influence on excessive alcohol drinking in a rodent model.